Association between a stromal cell-derived factor 1 (SDF-1/CXCL12) gene polymorphism and microvascular disease in systemic sclerosis.
OBJECTIVE
To investigate the possible implication of SDF1-3' polymorphism in systemic sclerosis (SSc) susceptibility or clinical phenotype, or both.


METHODS
150 patients with SSc and 150 controls were enrolled. Skin involvement, autoantibodies, interstitial lung disease, pulmonary arterial hypertension (PAH), scleroderma renal crisis, past and/or current skin ulcers were assessed. Genotyping was performed by PCR-RFLP.


RESULTS
Genotype distribution and allele frequency were similar in SSc and controls. SDF1-3'A allele and SDF1-3'GA/AA genotype frequencies were significantly higher in SSc-PAH than in SSc-non-PAH (33.3% vs 18.3%, p = 0.01) and in SSc with skin ulcers than in SSc without ulcers (27.3% vs 16.9%, p = 0.03). The SDF1-3'A allele influenced the predisposition to SSc-related PAH (OR = 2.52, 95% CI 1.11 to 5.69, p = 0.02) and skin ulcers (OR = 2.31, 95% CI 1.18 to 4.52, p = 0.01). After adjustment for age and gender, the SDF1-3'A allele remained a susceptibility factor for the SSc-related vascular manifestations (PAH: OR = 2.37, 95% CI 1.04 to 5.42, p = 0.04; ulcers: OR = 2.33, 95% CI 1.78 to 4.62, p = 0.01).


CONCLUSIONS
The SDF1-3'A allele is significantly associated with microvascular involvement in SSc.
Manetti
M
M
Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy.
Liakouli
V
V
Fatini
C
C
Cipriani
P
P
Bonino
C
C
Vettori
S
S
Guiducci
S
S
Montecucco
C
C
Abbate
R
R
Valentini
G
G
Matucci-Cerinic
M
M
Giacomelli
R
R
Ibba-Manneschi
L
L
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D054377:Chemokine CXCL12 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D055806:Microvessels; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D012595:Scleroderma, Systemic / Q000150:complications / Q000235:genetics* / Q000276:immunology; D012883:Skin Ulcer / Q000209:etiology* / Q000235:genetics
D001323:Autoantibodies; D054377:Chemokine CXCL12